Association studies for asthma and atopic diseases: a comprehensive review of the literature

Hundreds of genetic association studies on asthma-related phenotypes have been conducted in different populations. To date, variants in 64 genes have been reported to be associated with asthma or related traits in at least one study. Of these, 33 associations were replicated in a second study, 9 associations were not replicated either in a second study or a second sample in the same study, and 22 associations were reported in just a single published study. These results suggest the potential for a great amount of heterogeneity underlying asthma. However, many of these studies are methodologically limited and their interpretation hampered by small sample sizes

Risikorechnung bei industrieller Auftragsfertigung

Die Dynamik und Komplexität unternehmerischen Geschehens hat die Anzahl der Risiken erhöht und auch ihre Prognostizierbarkeit weiter beeinträchtigt. Davon sind im besonderen Maße Auftragsfertiger betroffen. Gerade Bauunternehmen haben in den vergangenen Jahren in erheblichem Umfang unerwartete Verluste hinnehmen müssen. Zur besseren Erfassung der Gefährdungspotentiale wird in dieser Arbeit das betriebliche Rechnungswesen um die Risikorechnung erweitert. Dabei handelt es sich um eine eigenständige Betrachtung von Risiken, die sämtliche risikorelevanten Informationen in einem Rechenkreis zusammenfrisikorelevanten Informationen in einem Rechenkreis zusammenführt. Oberstes Ziel ist eine genaue, über alle Aufträge konsistente und zeitnahe Messung, Überwachung und Steuerung von Risiken sowie eine bessere Kalkulation der Risikokosten. Dieses Buch wendet sich an Studierende mit Schwerpunkt Controlling beziehungsweise Baubetriebslehre sowie an interessierte Praktiker der Bauindustrie

Contemporary market structure and regulatory framework

This diagnosis of the European Parliament and of the Council points out that water is an economic good, but not a usual one. Water is vital for the people, animals and plants. Furthermore it is indispensable for the agriculture and industry. Nevertheless the water improvement incurs costs which have to be recovered. This poses special challenges to the water management and requires unique measures from an economic point of view. Cross countries the water industry is bound to an infrastructure which implicates its status as quasi natural monopoly. The lack of a competitive market pricing always implies a discussion of the competition in the water market. Furthermore the water sector is very capital intensive and has to face extremely high fixed costs. This raises the question of the right investment and funding strategies. As TRUST focuses on sustainable solutions, economical efficiency is one piece of the puzzle. The target of this report is to point out the status quo of the European water market and its regulatory framework. Collecting and analysing this general information with focus on the economic, financial aspects, is necessary to have a basis for possible further economic developments. First, the report will focus on the economic aspects of the European Water Framework Directive, which is valid for all EU countries. After a short, representative overview of the European water market and its regulatory framework the report will give a detailed look at the situation of the water sectors in Scotland, Germany, Portugal and Norway which are characterized by their differentiation. By mapping the European water supply situation in detailed country reports of four of the TRUST relevant case study cities this report creates the starting point for further tasks.Hoffjan, A.; Müller, NA. (2012). Contemporary market structure and regulatory framework. http://hdl.handle.net/10251/4662

Variation in genes encoding eosinophil granule proteins in atopic dermatitis patients from Germany

<p>Abstract</p> <p>Background</p> <p>Atopic dermatitis (AD) is believed to result from complex interactions between genetic and environmental factors. A main feature of AD as well as other allergic disorders is serum and tissue eosinophilia. Human eosinophils contain high amounts of cationic granule proteins, including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO) and major basic protein (MBP). Recently, variation in genes encoding eosinophil granule proteins has been suggested to play a role in the pathogenesis of allergic disorders. We therefore genotyped selected single nucleotide polymorphisms within the <it>ECP, EDN, EPO </it>and <it>MBP </it>genes in a cohort of 361 German AD patients and 325 healthy controls.</p> <p>Results</p> <p>Genotype and allele frequencies did not differ between patients and controls for all polymorphisms investigated in this study. Haplotype analysis did not reveal any additional information.</p> <p>Conclusion</p> <p>We did not find evidence to support an influence of variation in genes encoding eosinophil granule proteins for AD pathogenesis in this German cohort.</p

Financial sustainability rating tool for urban water systems

Solid financial position of water and wastewater utilities builds the basis for their sustainable services in the future, because it allows adequate investments into infrastructure renewal, technical innovations and ecological measures. The Financial Sustainability Rating Tool (FSRT) offers water supply and/or wastewater removal companies an opportunity to rate the utility's financial sustainability. It gives the user an indication, which area from financial situation over asset management to business operation needs optimization. The Tool also evaluates different forecasts (e.g. population development) and country specific characteristics (e.g. inflation rate) to assess future trends. Barometers with green to red indicators for each area as well as overall scores visualize the results of the web based rating. The Tool aims not to denounce a utility against others or to test its creditworthiness, but to encourage utilities to identify critical areas with respect to a solid financial position and to be open-minded for improvement actions. Accordingly, it has set itself the goal to uncover economic deficits and/or best practises to show the user where potentials for development are and which financial strategies are already viable for the future. To achieve meaningful results the Tool is directed at utilities, which provide either only one of the two services or are able to split up the information and costs related to each service.Hoffjan, A.; Di Federico, V.; Liserra, T.; Müller, N. (2014). Financial sustainability rating tool for urban water systems. http://hdl.handle.net/10251/3573

Advice to water management practitioners on competition, efficiency and new business opportunities

The water sector faces several challenges, which may demand a rethink of several important aspects within historically grown, traditional business models. The need for cost-effectiveness and the lack of public funding goes along with the emergence of new business opportunities. Under consideration of customer preferences, the competitive environment and the disassembling of the value chain, new business and organisational models to exploit service and technology niches are reviewed and recommended (e.g. based on price or product differentiation). This advice for water management practitioners shall help to ensure an adequate handling since competitive environment is establishing in the water sector. Therefore, the identification of the current level of efficiency within a utility as well as concrete measures for efficiency improvement are becoming increasingly important. Within this report special focus is placed on the role of business niches as well as on the possibilities of implementing business innovations. In this context, the design of enterprise-specific business models and its chances will be discussed.Hoffjan, A.; Müller, NA.; Di Federico, V.; Liserra, T. (2014). Advice to water management practitioners on competition, efficiency and new business opportunities. http://hdl.handle.net/10251/4662

Evaluation of the toll-like receptor 6 Ser249Pro polymorphism in patients with asthma, atopic dermatitis and chronic obstructive pulmonary disease

BACKGROUND: For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis'). Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases. We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD). METHODS: Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion. RESULTS: We found a weak association of the 249Ser allele with childhood asthma (p = 0.03). Yet, significance was lost after Bonferroni correction. No association was evident for AD or COPD. CONCLUSION: Variation in TLR6 might play a role in the pathogenesis of childhood asthma

Association of toll-interacting protein gene polymorphisms with atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disorder, affecting up to 15% of children in industrialized countries. Toll-interacting protein (TOLLIP) is an inhibitory adaptor protein within the toll-like receptor (TLR) pathway, a part of the innate immune system that recognizes structurally conserved molecular patterns of microbial pathogens, leading to an inflammatory immune response. METHODS: In order to detect a possible role of TOLLIP variation in the pathogenesis of AD, we screened the entire coding sequence of the TOLLIP gene by SSCP in 50 AD patients. We identified an amino acid exchange in exon 6 (Ala222Ser) and a synonymous variation in exon 4 (Pro139Pro). Subsequently, these two variations and four additional non-coding polymorphisms (-526 C/G, two polymorphisms in intron 1 and one in the 3'UTR) were genotyped in 317 AD patients and 224 healthy controls. RESULTS: The -526G allele showed borderline association with AD in our cohort (p = 0.012; significance level after correction for multiple testing 0.0102). Haplotype analysis did not yield additional information. Evaluation of mRNA expression by quantitative real-time polymerase chain reaction in six probands with the CC and six with the GG genotype at the -526 C/G locus did not reveal significant differences between genotypes. CONCLUSION: Variation in the TOLLIP gene may play a role in the pathogenesis of AD. Yet, replication studies in other cohorts and populations are warranted to confirm these association results

47 patients with FLNA associated periventricular nodular heterotopia

Background: Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. Methods: Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. Results: Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. Conclusions: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males